1. Field
The present disclosure relates generally to the fields of biology and medicine. More particularly, it concerns molecular interactions between human intelectins and microbial glycans. Specifically, the disclosure relates to the use of intelectins to identify and inhibit microbes.
2. Description of Related Art
Mammals place glycans on their cell surfaces that differ markedly from many of those present on microbes. Lectins that selectively recognize microbial glycans would be useful to distinguish between host and microbe, but the human lectins described to date can interact with human glycans. All cells are covered with a coat of glycans. Differences in the glycan coat can serve as markers of a cell's identity—its developmental state, its tissue type, or whether it is self- or non-self. To specifically recognize differences in glycosylation, humans use carbohydrate binding proteins, or lectins. The importance of glycosylation to human health is highlighted by the fact that 1-2% of the genes of any organism encode for enzymes predicted to be involved in glycosylation. Indeed, glycans are key biomolecules of molecular recognition.
Intelectins are a newly discovered class of animal lectins not similar to known C-type lectins (Drickamer, 1993), but nevertheless in many cases having been shown to bind carbohydrates in a calcium-dependent manner. The first intelectin protein was identified in Xenopus laevis oocytes and assigned the name XL-35 (Lee et al., 1997). Since then, homologs have been identified in a wide variety of animals; notable examples include lamprey, trout, sheep, mice and humans. Homologs of hIntL-1 are found in all mammals, suggesting that hIntL-1 is used by the hosts to identify microbial guests. Although intelectin family members share a high degree of sequence identity (FIGS. 5A-B), only a small 45 residue (residues 37-82 in hIntL-1 (Tsuji et al., 2001)) fibrinogen-like domain (FBD) shares sequence similarity to other proteins (Thomsen et al., 2011). In addition to intelectins, the FBD is found in other lectins, the best studied being innate immune lectins from the ficolin family. However, the predicted domain architecture and primary sequence differ significantly between intelectins and ficolins (FIGS. 6A-B).